Axl is a negative regulator of type I IFN in cDC1s hindering anti-tumor immunity

Background: The receptor tyrosine kinase Axl is widely implicated in tumor progression and immune evasion, yet its role in antitumor immunity remains poorly defined. Methods: Investigate the role of Axl on tumor growth, using animal models, genetic crosses, cellular assays, and single cell RNAseq from human and mouse tumors. Results: Here, we uncover Axl as a key negative regulator of type I interferon signaling in dendritic cells, with direct consequences for CD8⁺ T cell priming and tumor control. Axl-deficient mice exhibited delayed tumor growth that was dependent on CD8⁺ T cells and BATF3, highlighting a requirement for cross-presenting cDC1s. Conditional knockout models confirmed that Axl loss in dendritic cells-but not macrophages-was sufficient to enhance antitumor immunity through type I interferon pathways. Mechanistically, Axl ablation increased cDC1 cross-priming capacity and amplified the therapeutic effects of a STING agonist and radiotherapy. Conclusion: These findings position Axl as an intrinsic checkpoint in cDC1s that restrains interferon-driven immunity, revealing a mechanism by which innate regulation of dendritic cells shapes adaptive antitumor responses.